Small molecule developmental screens reveal the logic and timing of vertebrate development

Much has been learned about vertebrate development by random mutagenesis fo llowed by phenotypic screening and by targeted gene disruption followed by phenotypic analysis in model organisms. Because the timing of many developm ental events is critical, it would be useful to have temporal control over modulation of gene function, a luxury frequently not possible with genetic mutants. Here, we demonstrate that small molecules capable of conditional g ene product modulation can be identified through developmental screens in z ebrafish, We have identified several small molecules that specifically modu late various aspects of vertebrate ontogeny, including development of the c entral nervous system, the cardiovascular system, the neural crest, and the ear. Several of the small molecules identified allowed us to dissect the l ogic of melanocyte and otolith development and to identify critical periods for these events. Small molecules identified in this way offer potential t o dissect further these and other developmental processes and to identify n ovel genes involved in vertebrate development.